The Laryngeal and Speech Section investigates the control of laryngeal functioning in normal and disordered voice, speech and swallowing. Currently the Section has three projects addressing: 1) the role of sensory functioning in normal and disordered laryngeal control for voice and swallowing; 2) risk factors involved in familial speech and voice disorders; and 3) the use of neuromuscular stimulation to provide integrative control of the pharyngeal component of swallowing. Significant advances were made in the following directions: (1) Role of Sensory Functioning in Voice, Speech and Swallowing. Previously the Section demonstrated that patients with adductor spasmodic dysphonia, a laryngeal dystonia with spasmodic bursts in the thyroarytenoid muscles, had abnormal laryngeal responses to sensory conditioning. This suggested that abnormal modulation of sensorimotor repsonses might account for symptoms in this disorder. In the last year, the Section published a study in abductor spasmodic dysphonia, another form of laryngeal dystonia, demonstrating a similar abnormality in thyroarytenoid muscle responses to sensory stimulation in this disorder. Because the voice symptoms differ between these two forms of laryngeal dystonia, an ongoing study is investigating the muscle activation abnormalities during speech symptoms in abductor spasmodic dysphonia to determine how the pathophysiology of these two forms differ. Two studies were published this year on the neural substrates that may be involved in sensory control of vocalization. The nucleus tractus solitarius (NTS) is the primary termination zone for laryngeal afferents. The immunohistochemical distribution of alpha-amino-3- hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-selective glutamate receptor subunits (GluR1, GluR2/3, GluR4) and the N-methyl-D-aspartate (NMDA) receptor subunit NR1 in the caudal brainstem was investigated by using subunit-specific antibodies. Significant differences were found in the distribution of various receptor subunit types. GluR2/3 was highest in most subnuclei, while GluR1-containing neurons were more frequent than NR1- or GluR4-immunoreactive neurons. GluR1 immunolabeling was particularly high in the interstitial subnucleus, the region of the NTS previously found to be most active during elicitation of the early R1 adductor reflex. The second study examined neuronal activation in the periaquaductal gray (PAG), a midbrain region known to be involved in the generation of vocalization in animals. Two groups were contrasted: those receiving afferent stimulation resulting in the early R1 laryngeal adductor reflex, and control unstimulated animals. The number of neurons expressing Fos, the protein product of an immediate early gene c-fos, was examined in all PAG areas, including the dorsolateral and lateral regions which control vocalization functions. Comparisons between stimulated and control animals demonstrated increased fos expression associated with laryngeal stimulation only in the regions associated with vocalization and not in other PAG regions. How this sensory information normally alters vocalization patterns will be determined next. (2) Risk factors for Familial Voice and Speech Disorders. During the last 3 years, although the Section had recruited families with either adductor or abductor spasmodic dysphonia, only families with abductor spasmodic dysphonia were identified. All of the affected members are female with an earlier age of onset than found in the more common sporadic cases. The DYT1 mutation has been excluded in all of those tested thus far. (3) Development of a Laryngeal Neuroprosthesis for Dysphagia. The aim is to develop a neuroprosthesis for the prevention of aspiration in neurological disorders. A study was completed this year demonstrating the feasibility of stimulating the laryngeal muscles to produce dynamic control over laryngeal closure in animals. The implant remained fully functional for 6 months; laryngeal muscle characteristics were not adversely affected by chronic stimulation, and stable control over glottic closure was maintained. The next objective will be to achieve control over laryngeal elevation, similar to that occurring during normal swallowing in humans. - spasmodic dysphonia, voice, speech, swallowing, brainstem, sensorimotor control, familial disorders, neuroprosthesis - Human Subjects